The research to be undertaken is designed to shed light on the factors involved in cellular resistance to and recovery from virus infection. Among the problems to be studied are (1) persistent viral infections of cell lines with special emphasis on the selection of mutants with temperature-sensitive defects which may be involved in the establishment and maintenance of the persistently infected state; (2) the factors affecting the sensitivity of different viruses to interferon, specifically, the possible existence of separate and distinct resistance factors for RNA and DNA viruses; and (3) the control mechanisms involved in double infection of cells with two viruses, considering models in which the interaction leads to either facilitation or inhibition of the replication of one of the infecting viruses.